The overall aim of the project is to produce a set of psychophysical, physiological, and radiological techniques to aid in the diagnosis of olfactory dysfunction. These tools are designed to differentiate between peripheral conductive disorders and neural olfactory dysfunctions, on the one hand, and between olfactory mucosa and olfactory bulb dysfunctions, on the other hand. Specific Aim 1: Determine whether specific perturbations create their own psychophysical patterns of odorant misidentification nd dissimilarity. The extent to which specific medical and experimental manipulations induce consistent changes in psychophysical odorant object space as inferred from the olfactory Confusion matrix (OCM) and from psychophysical ratings of odorant dissimilarity using a labeled Magnitude Scale (LMS) will be determined. That is, are psychophysical responses altered in some consistent and predictable fashion by different perturbations? Specific Aim 2: Evaluate the effect of antecedent events on OCM patterns and lMS patterns - A prospective study. We will evaluate the capability of events in a patient's history to influence the PATTERNS of OCM an LMS responses. Specific Aim 3: Evaluate a technique to separate conductive and sensorineural dysfunctions in the diagnosis of hyposmia. An endoscopically guided odorant delivery system will be developed to quantify the relative contributions of sensorineural dysfunction and peripheral conductive loss. This delivery system will bypass peripheral conductive disorders in much the same way as bone conduction is used to evaluate conductive hearing loss. Specific Aim 4: Test the importance of the morphology of the nasal cavity, as opposed to its patency, on olfactory ability. A mathematical model will be developed to relate olfactory ability to morphology of the nasal cavity as an aid in the diagnosis of peripheral conductive disorders not related to patency. Specific Aim 5: Determine the functional status of the human olfactory epithelium with optical electrophysiological techniques. The techniques necessary to observe optically recorded odorant-induced activity patterns int he olfactory mucosa of normosmic humans will be developed. In addition, the relationship between mucosal activity patterns and disease processes will be examined. Specific Aim 6; Evaluate whether the volume of the olfactory bulb can be used as a reliable measure in the diagnosis of olfactory dysfunctions. Age and gender normative data on the size and dimensions of the olfactory bulb will be generated in normosmic subjects using MR imaging. These dimensions will be compared to the dimensions of olfactory bulbs in patients with Alzheimer's Disease. The relationship between olfactory ability will also be examined. This study proposes to investigate a wide range of techniques which might selectively tap and individually identify a number of mechanisms of dysosmia. In so doing, it aims to provide the necessary conceptual framework and technical strategy for further development of techniques to evaluate to evaluate the dysosmic patient.